Systems and methods for interior energy-activation from an exterior source

ABSTRACT

A method and a system for producing a change in a medium. The method places in a vicinity of the medium at least one energy modulation agent. The method applies an initiation energy to the medium. The initiation energy interacts with the energy modulation agent to directly or indirectly produce the change in the medium. The system includes an initiation energy source configured to apply an initiation energy to the medium to activate the energy modulation agent.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. Ser. No. 14/157,039 filedJan. 16, 2014. U.S. Ser. No. 14/157,039 is a continuation of U.S. Ser.No. 13/713,974 filed Dec. 13, 2012 which is a continuation of Ser. No.12/401,478 filed Mar. 10, 2009, the entire contents of each areincorporated herein by reference. This application is related toprovisional Ser. No. 60/910,663, filed Apr. 8, 2007, entitled “METHOD OFTREATING CELL PROLIFERATION DISORDERS,” and non-provisional Ser. No.11/935,655, filed Nov. 6, 2007, entitled “METHOD OF TREATING CELLPROLIFERATION DISORDERS,” the contents of each of which are herebyincorporated herein by reference. This application is related toprovisional Ser. No. 61/035,559, filed Mar. 11, 2008, entitled “SYSTEMSAND METHODS FOR INTERIOR ENERGY-ACTIVATION FROM AN EXTERIOR SOURCE,” theentire contents of which are hereby incorporated herein by reference.

THE NAMES OF THE PARTIES TO A JOINT RESEARCH AGREEMENT

Immunolight, LLC and Duke University are parties to a joint researchagreement in place at the time of the invention.

BACKGROUND OF THE INVENTION

1. Field of Invention

The invention relates to methods and systems for generating in theinterior of a medium or body radiant energy for producing a change inthe properties of a medium or body by exposure to the radiation.

2. Discussion of the Background

Presently, light (i.e., electromagnetic radiation from the radiofrequency through the visible to the x-ray and gamma ray wavelengthrange) activated processing is used in a number of industrial processesranging from photoresist curing, to on-demand ozone production, tosterilization, to the promotion of polymer cross-linking activation(e.g. in adhesive and surface coatings) and others. Today, lightactivated processing is seen in these areas to have distinct advantagesover more conventional approaches. For example, conventionalsterilization by steam autoclaving or in food processing bypasteurization may unsuitably overheat the medium to be sterilized. Assuch, light activated curable coatings are one of the fastest growingsectors in the coatings industry. In recent years, this technology hasmade inroads into a number of market segments like fiber optics, opticaland pressure-sensitive adhesives, and automotive applications like curedtopcoats, and curable powder coatings. The driving force of thisdevelopment is mostly the quest for an increase in productivity of thecoating and curing process, as conventional non light activated adhesiveand surface coatings typically require 1) the elimination of solventsfrom the adhesive and surface coatings to produce a cure and 2) atime/temperature cure which adds delay and costs to the manufacturingprocess.

Moreover, the use of solvent based products in adhesive and surfacecoatings applications is becoming increasingly unattractive because ofrising energy costs and stringent regulation of solvent emissions intothe atmosphere. Optimum energy savings as well as beneficial ecologicalconsiderations are both served by radiation curable adhesive and surfacecoating compositions. Radiation curable polymer cross-linking systemshave been developed to eliminate the need for high oven temperatures andto eliminate the need for expensive solvent recovery systems. In thosesystems, light irradiation initiates free-radical cross-linking in thepresence of common photo sensitizers.

However, in the adhesive and surface coating applications and in many ofthe other applications listed above, the light-activated processing islimited due to the penetration depth of light into the processed medium.For example, in water sterilization, ultraviolet light sources arecoupled with agitation and stirring mechanisms in order to ensure thatany bacteria in the water medium will be exposed to the UV light. Inlight-activated adhesive and surface coating processing, the primarylimitation is that the material to be cured must be directly exposed tothe light, both in type (wavelength or spectral distribution) andintensity. In adhesive and surface coating applications, any “shaded”area will require a secondary cure mechanism, increasing cure time overthe non-shaded areas and further delaying cure time due to the existentof a sealed skin through which subsequent curing must proceed (i.e.,referred to as a cocoon effect).

SUMMARY OF THE INVENTION

The invention overcomes the problems and disadvantages of the prior artas described in the various embodiments below.

In one embodiment, there is provided a method and system for producing achange in a medium disposed in an artificial container. The method (1)places in a vicinity of the medium an energy modulation agent, and (2)applies an initiation energy from an applied initiation energy sourcethrough the artificial container to the medium. The applied initiationenergy interacts with the energy modulation agent to directly orindirectly produce the change in the medium. The system includes theartificial container configured to contain the medium including theenergy modulation agent. The system further includes an appliedinitiation energy source configured to apply the initiation energythrough the artificial container to the medium to activate the energymodulation agent.

In another embodiment, there is provided a method and system for curinga radiation-curable medium. The method applies an applied energythroughout a composition including an uncured radiation-curable mediumand an energy modulation agent. The applied initiation energy interactswith the energy modulation agent to directly or indirectly cure themedium by polymerization of polymers in the medium. The system includesan initiation energy source configured to apply initiation energy to thecomposition.

It is to be understood that both the foregoing general description ofthe invention and the following detailed description are exemplary, butare not restrictive of the invention.

BRIEF DESCRIPTION OF THE FIGURES

A more complete appreciation of the invention and many of the attendantadvantages thereof will be readily obtained as the same becomes betterunderstood by reference to the following detailed description whenconsidered in connection with the accompanying drawings, wherein:

FIG. 1 provides an exemplary electromagnetic spectrum in meters (1 nmequals 10⁻⁹ meters);

FIG. 2 is a table providing a list of photoactivatable agents;

FIG. 3A is a schematic depicting a system according to one embodiment ofthe invention in which an initiation energy source is directed to aself-contained medium for producing changes in the medium;

FIG. 3B is a schematic depicting a system according to anotherembodiment of the invention in which the initiation energy source isdirected to a container enclosing a medium having energy modulationagents disbursed within the medium;

FIG. 3C is a schematic depicting a system according to anotherembodiment of the invention in which the initiation energy source isdirected to a container enclosing a medium having energy modulationagents segregated within the medium;

FIG. 3D is a schematic depicting a system according to anotherembodiment of the invention in which the initiation energy source isdirected to a container enclosing a medium having energy modulationagents segregated within the medium in a fluidized bed configuration;

FIG. 4 illustrates an exemplary computer system for implementing variousembodiments of the invention;

DETAILED DESCRIPTION OF THE INVENTION

The invention sets forth a novel method for causing a change in activityof an in a medium that is effective, specific, and able to produce achange to the medium.

Generally, the invention provides methods for producing a change in amedium after generation of radiant light inside the medium. In thismethod, an initiation energy source provides an initiation energy thatpenetrates the medium and induces internal radiation to produce adesired effect in the medium.

In one embodiment, the initiation energy source is applied directly orindirectly to the medium. Within the context of the invention, thephrase “applied indirectly” (or variants of this phrase, such as“applying indirectly”, “indirectly applies”, “indirectly applied”,“indirectly applying”, etc.), when referring to the application of theinitiation energy, means the penetration by the initiation energy intothe medium beneath the surface of the medium and to the activatableagent or energy modulation agents within a medium. In one embodiment,the initiation energy interacts with a previously supplied energymodulation agent which then activates the activatable agent.

Although not intending to be bound by any particular theory or beotherwise limited in any way, the following theoretical discussion ofscientific principles and definitions are provided to help the readergain an understanding and appreciation of the invention.

As used herein, an “activatable agent” is an agent that normally existsin an inactive state in the absence of an activation signal. When theagent is activated by an activation signal under activating conditions,the agent is capable of producing a desired pharmacological, cellular,chemical, electrical, or mechanical effect in a medium (i.e. apredetermined change). For example, when photocatalytic agents areirradiated with visible or UV light, these agents induce polymerizationand “curing” of light sensitive adhesives.

Signals that may be used to activate a corresponding agent may include,but are not limited to, photons of specific wavelengths (e.g. x-rays, orvisible light), electromagnetic energy (e.g. radio or microwave),thermal energy, acoustic energy, or any combination thereof. Activationof the agent may be as simple as delivering the signal to the agent ormay further require a set of activation conditions. For example, anactivatable agent, such as a photosensitizer, may be activated by UV-Aradiation (e.g., by UV-A radiation generated internally in the medium).Once activated, the agent in its active-state may then directly proceedto produce a predetermined change.

Where activation may further require other conditions, mere delivery ofthe activation signal may not be sufficient to bring about thepredetermined change. For example, a photoactive compound that achievesits effect by binding to certain structure in its active state mayrequire physical proximity to the target structure when the activationsignal is delivered. For such activatable agents, delivery of theactivation signal under non-activating conditions will not result in thedesired effect. Some examples of activating conditions may include, butare not limited to, temperature, pH, location, state of the medium, andthe presence or absence of co-factors.

Selection of an activatable agent greatly depends on a number of factorssuch as the desired change, the desired form of activation, as well asthe physical and biochemical constraints that may apply. Exemplaryactivatable agents may include, but are not limited to agents that maybe activated by photonic energy, electromagnetic energy, acousticenergy, chemical or enzymatic reactions, thermal energy, microwaveenergy, or any other suitable activation mechanisms.

When activated, the activatable agent may effect changes that include,but are not limited to an increase in organism activity, a fermentation,a decrease in organism activity, apoptosis, redirection of metabolicpathways, a sterilization of a medium, a cross polymerization and curingof a medium, or a cold pasteurization of a medium.

The mechanisms by which an activatable agent may achieve its desiredeffect are not particularly limited. Such mechanisms may include directaction on a predetermined target as well as indirect actions viaalterations to the biochemical pathways. In one embodiment, theactivatable agent is capable of chemically binding to the organism in amedium. In this embodiment, the activatable agent, is exposed in situ toan activating energy emitted from an energy modulation agent, which, inturn receives energy from an initiation energy source.

Suitable activatable agents include, but are not limited to, photoactiveagents, sono-active agents, thermo-active agents, andradio/microwave-active agents. An activatable agent may be a smallmolecule; a biological molecule such as a protein, a nucleic acid orlipid; a supramolecular assembly; a nanoparticle; or any other molecularentity capable of producing a predetermined activity once activated.

The activatable agent may be derived from a natural or synthetic origin.Any such molecular entity that may be activated by a suitable activationsignal source to effect a predetermined cellular change may beadvantageously employed in the invention.

Suitable photoactive agents include, but are not limited to: psoralensand psoralen derivatives, pyrene cholesteryloleate, acridine, porphyrin,fluorescein, rhodamine, 16-diazorcortisone, ethidium, transition metalcomplexes of bleomycin, transition metal complexes of deglycobleomycin,organoplatinum complexes, alloxazines such as 7,8-dimethyl-10-ribitylisoalloxazine (riboflavin), 7,8,10-trimethylisoalloxazine (lumiflavin),7,8-dimethylalloxazine (lumichrome), isoalloxazine-adenine dinucleotide(flavine adenine dinucleotide [FAD]), alloxazine mononucleotide (alsoknown as flavine mononucleotide [FMN] and riboflavine-5-phosphate),vitamin Ks, vitamin L, their metabolites and precursors, andnapththoquinones, naphthalenes, naphthols and their derivatives havingplanar molecular conformations, porphyrins, dyes such as neutral red,methylene blue, acridine, toluidines, flavine (acriflavinehydrochloride) and phenothiazine derivatives, coumarins, quinolones,quinones, and anthroquinones, aluminum (111) phthalocyaninetetrasulfonate, hematoporphyrin, and phthalocyanine, and compounds whichpreferentially adsorb to nucleic acids with little or no effect onproteins. The term “alloxazine” includes isoalloxazines.

Endogenously-based derivatives include synthetically derived analogs andhomologs of endogenous photoactivated molecules, which may have or lacklower (1 to 5 carbons) alkyl or halogen substitutes of thephotosensitizers from which they are derived, and which preserve thefunction and substantial non-toxicity. Endogenous molecules areinherently non-toxic and may not yield toxic photoproducts afterphotoradiation.

FIG. 1 provides an exemplary electromagnetic spectrum in meters (1 nmequals 1 nanometer). As used herein, an “energy modulation agent” refersto an agent that is capable of receiving an energy input from a sourceand then re-emitting a different energy to a receiving target. Energytransfer among molecules may occur in a number of ways. The form ofenergy may be electronic, thermal, electromagnetic, kinetic, or chemicalin nature. Energy may be transferred from one molecule to another(intermolecular transfer) or from one part of a molecule to another partof the same molecule (intramolecular transfer). For example, amodulation agent may receive electromagnetic energy and re-emit theenergy in the form of thermal energy.

Table 1 in FIG. 2 provides a list of photoactivatable agents that may beused as primary or secondary internal light sources. For example, thephotoactivatable agents could be receptors of X-ray induced emissionsfrom nanoparticles (to be discussed later) and which in turn emit asecondary light. In some mediums, it may be that the excitationwavelengths in Table 1 are transparent to the particular medium and theemission wavelengths are highly absorbent (due to, for example,molecular or solid state band gap transitions). In those cases, thephotoreactive agents in Table 1 would be the primary sources forinternal light generation.

In various embodiments, the energy modulation agent receives higherenergy (e.g. x-ray) and re-emits in lower energy (e.g. UV-A). Somemodulation agents may have a very short energy retention time (on theorder of fs, e.g. fluorescent molecules) whereas others may have a verylong half-life (on the order of minutes to hours, e.g. luminescent orphosphorescent molecules). Suitable energy modulation agents include,but are not limited to, a biocompatible fluorescing metal nanoparticle,fluorescing dye molecule, gold nanoparticle, a water soluble quantum dotencapsulated by polyamidoamine dendrimers, a luciferase, a biocompatiblephosphorescent molecule, a combined electromagnetic energy harvestermolecule, and a lanthanide chelate capable of intense luminescence.Typically, the energy modulation agents induce photoreactive changes inthe medium and are not used for the purpose of exclusively heating themedium.

Various exemplary uses are described in the embodiments below.

The modulation agents may further be coupled to a carrier for targetingpurposes. For example, a biocompatible molecule, such as a fluorescingmetal nanoparticle or fluorescing dye molecule that emits in the UV-Aband, may be selected as the energy modulation agent. The energymodulation agent may be preferably directed to the desired site bysystemic administration into a medium. For example, a UV-A emittingenergy modulation agent may be distributed in the medium by physicalinsertion and or mixing, or by conjugating the UV-A emitting energymodulation agent with a specific carrier, such as a lipid, chitin orchitin-derivative, a chelate or other functionalized carrier that iscapable of concentrating the UV-A emitting source in a specific targetregion of the medium.

Additionally, the energy modulation agent can be used alone or as aseries of two or more energy modulation agents such that the energymodulation agents provide an energy cascade. Thus, the first energymodulation agent in the cascade will absorb the activation energy,convert it to a different energy which is then absorbed by the secondenergy modulation in the cascade, and so forth until the end of thecascade is reached with the final energy modulation agent in the cascadeemitting the energy necessary to activate the activatable agent.Alternatively, one or more energy modulation agents in the cascade mayalso activate additional activatable agents.

Although the activatable agent and the energy modulation agent can bedistinct and separate, it will be understood that the two agents neednot be independent and separate entities. In fact, the two agents may beassociated with each other via a number of different configurations.Where the two agents are independent and separately movable from eachother, they can generally interact with each other via diffusion andchance encounters within a common surrounding medium. Where theactivatable agent and the energy modulation agent are not separate, theymay be combined into one single entity.

The initiation energy source can be any energy source capable ofproviding energy at a level sufficient to activate the activatable agentdirectly, or to provide the energy modulation agent with the inputneeded to emit the activation energy for the activatable agent (indirectactivation). Preferable initiation energy sources include, but are notlimited to, ultraviolet lamps such as UV-A and UV-B lamps, halogenlamps, fiber optic lines, a light needle, an endoscope, self-ballastedmercury vapor lamps, ballasted HID lamps, and any device capable ofgenerating x-ray, y-ray, gamma-ray, or electron beams.

In one embodiment, the initiation energy is capable of penetratingcompletely through the medium. Within the context of the invention, thephrase “capable of penetrating completely through the medium” is used torefer to energy capable of penetrating a container to any distancenecessary to activate the activatable agent within the medium. It is notrequired that the energy applied actually pass completely through themedium, merely that it be capable of doing so in order to permitpenetration to any desired distance to activate the activatable agent.The type of energy source chosen will depend on the medium itself.Exemplary initiation energy sources that are capable of penetratingcompletely through the medium include, but are not limited to, x-rays,gamma rays, electron beams, microwaves and radio waves.

In one embodiment, the source of the initiation energy can be aradiowave emitting nanotube, such as those described by K. Jensen, J.Weldon, H. Garcia, and A. Zettl in the Department of Physics at theUniversity of California at Berkeley (seehttp://socrates.berkeley.edu/˜argon/nanoradio/radio.html, the entirecontents of which are hereby incorporated by reference). These nanotubescan be introduced to the medium, and preferably would be coupled to theactivatable agent or the energy modulation agent, or both, such thatupon application of the initiation energy, the nanotubes would acceptthe initiation energy (preferably radiowaves), then emit radiowaves inclose proximity to the activatable agent, or in close proximity to theenergy modulation agent, to then cause activation of the activatableagent. In such an embodiment, the nanotubes would act essentially as aradiowave focusing or amplification device in close proximity to theactivatable agent or energy modulation agent.

Alternatively, the energy emitting source may be an energy modulationagent that emits energy in a form suitable for absorption by a transferagent or for direct interaction with components of the medium. Forexample, the initiation energy source may be acoustic energy, and oneenergy modulation agent may be capable of receiving acoustic energy andemitting photonic energy (e.g. sonoluminescent molecules) to be receivedby another energy modulation agent that is capable of receiving photonicenergy. Other examples include transfer agents that receive energy atx-ray wavelength and emit energy at UV wavelength, preferably at UV-Awavelength. As noted above, a plurality of such energy modulation agentsmay be used to form a cascade to transfer energy from initiation energysource via a series of energy modulation agents to activate theactivatable agent.

Photoactivatable agents may be stimulated by an energy source throughmechanisms such as irradiation, resonance energy transfer, excitonmigration, electron injection, or chemical reaction, to an activatedenergy state that is capable of producing the predetermined changedesired. One advantage is that wavelengths of emitted radiation may beused to selectively stimulate one or more photoactivatable agents orenergy modulation agents capable of stimulating the one or morephotoactivatable agents. The energy modulation agent is suitablystimulated at a wavelength and energy that causes little or no change tothe medium.

In another embodiment, the photoactivatable agent is stimulated via aresonance energy transfer. Resonance Energy Transfer (RET) is an energytransfer mechanism between two molecules having overlapping emission andabsorption bands. Electromagnetic emitters are capable of converting anarriving wavelength to a longer wavelength. For example, UV-B energyabsorbed by a first molecule may be transferred by a dipole-dipoleinteraction to a UV-A-emitting molecule in close proximity to theUV-B-absorbing molecule. One advantage is that multiple wavelengths ofemitted radiation may be used to selectively stimulate one or morephotoactivatable agents or energy modulation agents capable ofstimulating the one or more photoactivatable agents. With RET, theenergy modulation agent is preferably stimulated at a wavelength andenergy that causes little or no effect to the surrounding medium withthe energy from one or more energy modulation agents being transferred,such as by Foerster Resonance Energy Transfer, to the photoactivatableagents.

Alternatively, a material absorbing a shorter wavelength may be chosento provide RET to a non-emitting molecule that has an overlappingabsorption band with the transferring molecule's emission band.Alternatively, phosphorescence, chemiluminescence, or bioluminescencemay be used to transfer energy to a photoactivatable molecule.

Alternatively, one can apply the initiation energy source to the medium.Within the context of the invention, the applying of the initiationenergy source means the application of an agent, that itself producesthe initiation energy, in a manner that permits the agent to arrive atthe target structure within the medium. In this embodiment, theinitiation energy source includes, but is not limited to, chemicalenergy sources, nanoemitters, nanochips, and other nanomachines thatproduce and emit energy of a desired frequency.

Recent advances in nanotechnology have provided examples of variousdevices that are nanoscale and produce or emit energy, such as theMolecular Switch (or Mol-Switch) work by Dr. Keith Firman of the ECResearch and Development Project, or the work of Cornell et al. (1997)who describe the construction of nanomachines based around ion-channelswitches only 1.5 nm in size, which use ion channels formed in anartificial membrane by two gramicidin molecules: one in the lower layerof the membrane attached to a gold electrode and one in the upper layertethered to biological receptors such as antibodies or nucleotides. Whenthe receptor captures a target molecule or cell, the ion channel isbroken, its conductivity drops, and the biochemical signal is convertedinto an electrical signal. These nanodevices could also be coupled withthe invention to provide targeting of the target cell, to deliver theinitiation energy source directly at the desired site.

In another embodiment, the invention includes the application of theactivatable agent, along with a source of chemical energy such aschemiluminescence, phosphorescence or bioluminescence. The source ofchemical energy can be a chemical reaction between two or morecompounds, or can be induced by activating a chemiluminescent,phosphorescent or bioluminescent compound with an appropriate activationenergy, either outside the medium or inside the medium, with thechemiluminescence, phosphorescence or bioluminescence being allowed toactivate the activatable agent in the medium. The administration of theactivatable agent and the source of chemical energy can be performedsequentially in any order or can be performed simultaneously.

In the case of certain sources of such chemical energy, the applicationof the chemical energy source can be performed after activation outsidethe medium, with the lifetime of the emission of the energy being up toseveral hours for certain types of phosphorescent materials for example.

Yet another example is that nanoparticles or nanoclusters of certainatoms may be introduced such that they are capable of resonance energytransfer over comparatively large distances, such as greater than onenanometer, more preferably greater than five nanometers, even morepreferably at least 10 nanometers. Functionally, resonance energytransfer may have a large enough “Foerster” distance (R₀), such thatnanoparticles in one part of a medium are capable of stimulatingactivation of photoactivatable agents disposed in a distant portion ofthe medium, so long as the distance does not greatly exceed R₀. Forexample, gold nanospheres having a size of 5 atoms of gold have beenshown to have an emission band in the ultraviolet range, recently.

Any of the photoactivatable agents may be exposed to an excitationenergy source provided in the medium. The photoactive agent may bedirected to a receptor site by a carrier having a strong affinity forthe receptor site. Within the context of the invention, a “strongaffinity” is preferably an affinity having an equilibrium dissociationconstant, K_(i), at least in the nanomolar, nM, range or higher. Thecarrier may be a polypeptide and may form a covalent bond with aphotoactive agent, for example. Alternatively, a photoactive agent mayhave a strong affinity for the target molecule in the medium withoutbinding to a carrier.

In one embodiment, a plurality of sources for supplying electromagneticradiation energy or energy transfer is provided by one or more moleculesprovided to the medium. The molecules may emit stimulating radiation inthe correct band of wavelength to stimulate the photoactivatable agents,or the molecules may transfer energy by a resonance energy transfer orother mechanism directly to the photoactivatable agent or indirectly bya cascade effect via other molecular interactions.

In a further embodiment, a biocompatible emitting source, such as afluorescing metal nanoparticle or fluorescing dye molecule, is selectedthat emits in the UV-A band. UV-A and the other UV bands are known to beeffective as germicides.

In one embodiment, the UV-A emitting source is a gold nanoparticlecomprising a cluster of 5 gold atoms, such as a water soluble quantumdot encapsulated by polyamidoamine dendrimers. The gold atom clustersmay be produced through a slow reduction of gold salts (e.g. HAuCl₄ orAuBr₃) or other encapsulating amines, for example. One advantage of sucha gold nanoparticle is the increased Foerster distance (i.e. R₀), whichmay be greater than 100 angstroms. The equation for determining theFoerster distance is substantially different from that for molecularfluorescence, which is limited to use at distances less than 100angstroms. It is believed that the gold nanoparticles are governed bynanoparticle surface to dipole equations with a 1/R⁴ distance dependencerather than a 1/R⁶ distance dependence. For example, this permitscytoplasmic to nuclear energy transfer between metal nanoparticles and aphotoactivatable molecule.

In another embodiment, a UV or light-emitting luciferase is selected asthe emitting source for exciting a photoactivatable agent. A luciferasemay be combined with molecules, which may then be oxygenated withadditional molecules to stimulate light emission at a desiredwavelength. Alternatively, a phosphorescent emitting source may be used.Phosphorescent materials may have longer relaxation times thanfluorescent materials, because relaxation of a triplet state is subjectto forbidden energy state transitions, storing the energy in the excitedtriplet state with only a limited number of quantum mechanical energytransfer processes available for returning to the lower energy state.Energy emission is delayed or prolonged from a fraction of a second toseveral hours. Otherwise, the energy emitted during phosphorescentrelaxation is not otherwise different than fluorescence, and the rangeof wavelengths may be selected by choosing a particular phosphor.

In another embodiment, a combined electromagnetic energy harvestermolecule is designed, such as the combined light harvester disclosed inJ. Am. Chem. Soc. 2005, 127, 9760-9768, the entire contents of which arehereby incorporated by reference. By combining a group of fluorescentmolecules in a molecular structure, a resonance energy transfer cascademay be used to harvest a wide band of electromagnetic radiationresulting in emission of a narrow band of fluorescent energy. By pairinga combined energy harvester with a photoactivatable molecule, a furtherenergy resonance transfer excites the photoactivatable molecule, whenthe photoactivatable molecule is nearby stimulated combined energyharvester molecules. Another example of a harvester molecule isdisclosed in FIG. 4 of “Singlet-Singlet and Triplet-Triplet EnergyTransfer in Bichromophoric Cyclic Peptides,” M. S. Thesis by M. O.Guler, Worcester Polytechnic Institute, May 18, 2002, which isincorporated herein by reference.

In another embodiment, a Stokes shift of an emitting source or a seriesof emitting sources arranged in a cascade is selected to convert ashorter wavelength energy, such as X-rays, to a longer wavelengthfluorescence emission such a optical or UV-A, which is used to stimulatea photoactivatable molecule in the medium.

In an additional embodiment, the photoactivatable agent can be aphotocaged complex having an active agent (which can be a cytotoxicagent if cytotoxicity is needed, or can be an activatable agent)contained within a photocage. In various embodiments, where the activeagent is a cyotoxic agent, the photocage molecule releases the cytotoxicagent into the medium where it can attack non-beneficial “target”species in the medium. The active agent can be bulked up with othermolecules that prevent it from binding to specific targets, thus maskingits activity. When the photocage complex is photoactivated, the bulkfalls off, exposing the active agent. In such a photocage complex, thephotocage molecules can be photoactive (i.e. when photoactivated, theyare caused to dissociate from the photocage complex, thus exposing theactive agent within), or the active agent can be the photoactivatableagent (which when photoactivated causes the photocage to fall off), orboth the photocage and the active agent are photoactivated, with thesame or different wavelengths. Suitable photocages include thosedisclosed by Young and Deiters in “Photochemical Control of BiologicalProcesses”, Org. Biomol. Chem., 5, pp. 999-1005 (2007) and“Photochemical Hammerhead Ribozyme Activation”, Bioorganic & MedicinalChemistry Letters, 16(10), pp. 2658-2661 (2006), the contents of whichare hereby incorporated by reference.

Work has shown that the amount of singlet oxygen necessary to cause celllysis, and thus cell death, is 0.32 H 10⁻³ mol/liter or more, or 10⁹singlet oxygen molecules/cell or more. In one embodiment of theinvention, the level of singlet oxygen production caused by theinitiation energy or the activatable agent upon activation is sufficientto cause a change in a medium, wherein the medium becomes free from anymicroorganisms. Microorganisms include but are not limited to bacteria,viruses, yeasts or fungi. To this end, singlet oxygen in sufficientamounts as described above can be used to sterilize the medium.

For example, medical bottle caps need to be sterilized between the basecap material and the glued seal material which contacts the base of themedical bottle. Because steam autoclaves are insufficient for thispurpose, one embodiment of the invention uses UV luminescing particlesincluded in the adhesive layer when the seal material is applied to thebottle cap. Then, X-ray irradiation becomes capable of curing theadhesive and producing within the adhesive medium UV radiation fordirect sterilization or the production of singlet oxygen or ozone forbiological germicide.

The activatable agent and derivatives thereof as well as the energymodulation agent, can be incorporated into compositions suitable fordelivery to particular mediums. The composition can also include atleast one additive having a complementary effect upon the medium, suchas a lubricant or a sealant.

The carrier can be a solvent or dispersion medium containing, forexample, water, ethanol, polyol (for example, glycerol, propyleneglycol, and liquid polyethylene glycol, and the like), and suitablemixtures thereof. The proper fluidity can be maintained, for example, bythe use of a coating such as lecithin, by the maintenance of therequired particle size in the case of dispersion and by the use ofsurfactants.

Referring to FIG. 3A, an exemplary system according to one embodiment ofthe invention may have an initiation energy source 1 directed at medium4. Activatable agents 2 and an energy modulation agents 3 are dispersedthroughout the medium 4. The initiation energy source 1 may additionallybe connected via a network 8 to a computer system 5 capable of directingthe delivery of the initiation energy. In various embodiments, theenergy modulation agents 3 are encapsulated energy modulation agents 6,depicted in FIG. 3A as silica encased energy modulation agents. As shownin FIG. 3A, initiation energy 7 in the form of radiation from theinitiation energy source 1 permeated throughout the medium 4. A morethorough discussion of the computer system 5 is provided below inreference to FIG. 4. As discussed below in more detail, the initiationenergy source 1 can be an external energy source or an energy sourcelocated at least partially in the medium 4.

In various embodiments, the initiation energy source 1 may be a linearaccelerator equipped with image guided computer-control capability todeliver a precisely calibrated beam of radiation to a pre-selectedcoordinate. One example of such linear accelerators is the SmartBeam™IMRT (intensity modulated radiation therapy) system from Varian medicalsystems (Varian Medical Systems, Inc., Palo Alto, Calif.). In otherembodiments, the initiation energy source 1 may be commerciallyavailable components of X-ray machines or non-medical X-ray machines.X-ray machines that produce from 10 to 150 keV X-rays are readilyavailable in the marketplace. For instance, the General ElectricDefinium series or the Siemens MULTIX series are but two examples oftypical X-ray machines designed for the medical industry, while theEagle Pack series from Smith Detection is an example of a non-medicalX-ray machine. As such, the invention is capable of performing itsdesired function when used in conjunction with commercial X-rayequipment.

In other embodiments, the initiation energy source 1 can be a radiofrequency or microwave source emitting radio waves at a frequency whichpermeates the medium and which triggers or produces secondary radiantenergy emission within the medium by interaction with the energymodulation elements 6 therein. In other embodiments, the initiationenergy source 1 can be an ultraviolet, visible, near infrared (NIR) orinfrared (IR) emitter emitting at a frequency which permeates the medium4 and which triggers or produces secondary radiant energy emissionwithin medium 4 by interaction with the energy modulation elements 6therein.

FIG. 3B is a schematic depicting another system according to anotherembodiment of the invention in which the initiation energy source 1 ofFIG. 3A is directed to energy modulation elements 6 placed in thevicinity of a fluid medium 4 (e.g., a liquid or other fluid-like medium)and held inside a container 9. The container 9 is made of a materialthat is “transparent” to the radiation 7. For example, plastic, quartz,glass, or aluminum containers would be sufficiently transparent toX-rays, while plastic or quartz or glass containers would be transparentto microwave or radio frequency light. The energy modulation elements 6can be dispersed uniformly throughout the medium or may be segregated indistinct parts of the medium or further separated physically from themedium by encapsulation structures 10. A supply 11 provides the medium 4to the container 9.

Alternatively, as shown in FIG. 3C, the luminescing particles could bepresent in the medium in encapsulated structures 10. In one embodiment,the encapsulated structures 10 are aligned with an orientation in linewith the external initiation energy source 1. In this configuration,each of the encapsulated structures 10 has itself a “line-of-sight” tothe external initiation energy source 1 shown in FIG. 3C without beingoccluded by other of the encapsulated structures 10. In otherembodiments, the encapsulated structures 10 are not so aligned in thatdirection, but could aligned perpendicular to the direction shown inFIG. 3C, or could be randomly placed. Indeed, supply of fluid medium 4could itself be used to agitate the encapsulated structures 10 and mixthe fluid medium 4 inside container 9.

The system of FIG. 3C may also be used without energy modulation agents.In this embodiment, the initiation energy source 1 can be for example atan energy suitable for driving physical, chemical, and/or biologicalprocesses in the fluid medium 4. In one aspect of the invention, theinitiation energy source 1 can a UV light source as in many conventionalUV sterilization systems and the encapsulated structures 10 of FIG. 3Care light rods conducting UV light from an exterior source to a regioninside the medium 4. In one aspect of the invention, the initiationenergy source 1 can be even disposed inside the medium and can be a UVlight source as in many conventional UV sterilization systems.

FIG. 3D is a schematic depicting a system according to anotherembodiment of the invention in which the initiation energy source isdirected a container enclosing a medium having energy modulation agentssegregated within the medium in a fluidized bed 20 configuration. Thefluidized bed 20 includes the encapsulated structures 10 in aconfiguration where a fluid to be treated is passed between theencapsulated structures 10.

In further embodiments of the invention, robotic manipulation devicesmay also be included in the systems of FIGS. 3A, 3B, 3C, and 3D for thepurpose of delivering and dispersing the energy modulation elements 6 inmedium 4 or for the purpose of removing old product and introducing newproduct for treatment into the system.

Commercial Applications

In the following commercial applications of the invention describedhere, the energy modulation agents 3 (e.g., luminescing particles orphoton emitters) are provided and distributed into a medium 4 fordeactivation or activation of agents in the medium to produce aphysical, chemical, or biological change in the medium.

Examples of luminescing particles can include gold particles (such asfor example the nanoparticles of gold described above), BaFBr:Euparticles, CdSe particles, Y₂O₃:Eu³⁺ particles, and/or other knownstimulated luminescent materials such as for example ZnS:Mn²⁺; ZnS:Mn²⁺,Yb³⁺, Y₂O₃:Eu³⁺; BaFBr:Tb³⁺; and YF₃:Tb³+.

In one embodiment of the invention described here, other potentiallyuseful luminescing particles (or energy modulation agents) includecarbon nanotubes as described for example by Wang et al. in“Electromagnetic excitation of nano-carbon in vacuum,” in OPTICSEXPRESS, Vol. 13, No. 10, May 10, 2005, the entire contents of which areincorporated herein by reference. Such carbon nanotubes show both blackbody emission and discrete line-type emissions in the visible whenexposed to microwave irradiation.

Other potentially useful luminescing particles for the inventiondescribed here include the chemiluminescent reactions/species describedby Aslan et al. in “Multicolor Microwave-Triggered Metal-EnhancedChemiluminescence,” in J. AM. CHEM. SOC. published on Web Sep. 23, 2006,the entire contents of which are incorporated herein by reference. Thesechemiluminescent reactions/species are formed with silver nanoparticleswhich enhance the chemiluminescent reactions when exposed to microwaveradiation. Aslan et al. utilized chemiluminescent species fromcommercial glow sticks where for example hydrogen peroxide oxidizesphenyl oxalate ester to a peroxyacid ester and phenol. The unstableperoxyacid ester decomposes to a peroxy compound and phenol, the processchemically inducing an electronic excited state responsible for thelight emission. While these chemiluminescent species will have a limitedlifetime, there use in curing applications for the invention describedhere is still viable where the cure process is a one-time occurrence,and the external microwave source accelerates the cure by acceleratedvisible light production.

The luminescent wavelength and/or efficiency of the luminescentparticles often depend on the size of the particle. Particle sizes inthe nanometer size range for the invention described here exhibitstronger luminescence in many cases, as described in U.S. Pat. Appl.Publ. No. 2007/0063154, whose entire contents are incorporated herein byreference. Further, in one embodiment of the invention described here,the luminescing particles can be combined with molecular complexes suchas poly(ethylene glycol), vitamin B12, or DNA, which serves to mitigateagainst coagulation of the luminescing particles (especially thenanoparticles) and serves to make the luminescing particlesbiocompatible. More specifically, one recipe for the synthesis of CdSenanocrystals is given here from U.S. Pat. Appl. Publ. No. 2007/0063154.Accordingly, citrate-stabilized CdSe nanocrystals suitable for theinvention described here can be prepared according to the followingprocedure:

-   -   To 45 ml of water are added 0.05 g sodium citrate (Fluka) and 2        ml of 4×10⁻²M cadmium perchlorate (Aldrich). The pH is adjusted        to 9.0 by 0.1 M NaOH (Alfa). The solution is bubbled with        nitrogen for 10 minutes, and then 2 ml of 1×10⁻²M        N,N-dimethylselenourea (Alfa) is added. The mixture is heated in        a conventional 900-watt microwave oven for 50 seconds. In this        recipe, the Cd:Se molar ratio is 4:1, which leads to CdSe        nanoparticles with ^(˜)4.0 nm diameter; by increasing the Cd        concentration it is possible to synthesize smaller CdSe        nanoparticles.

Further, the luminescing particles for the invention described here canbe coated with insulator materials such as for example silica which willreduce the likelihood of any chemical interaction between theluminescing particles and the medium. For biological applications ofinorganic nanoparticles, one of the major limiting factors is theirtoxicity. Generally speaking, all semiconductor nanoparticles are moreor less toxic. For biomedical applications, nanoparticles with toxicityas low as possible are desirable or else the nanoparticles have toremain separated from the medium. Pure TiO₂, ZnO, and Fe₂O₃ arebiocompatible. CdTe and CdSe are toxic, while ZnS, CaS, BaS, SrS andY₂O₃ are less toxic. In addition, the toxicity of nanoparticles canresult from their inorganic stabilizers, such as TGA, or from dopantssuch as Eu²⁺, Cr³⁺ or Nd³⁺.

To reduce the toxicity or to make these nanoparticles bio-inert orbiocompatible, one embodiment of the invention described here coatsthese nanoparticles with silica. Silica is used as a coating material ina wide range of industrial colloid products from paints and magneticfluids to high-quality paper coatings. Further, silica is bothchemically and biologically inert and also is optically transparent. Inthe following recipe (from M A. Correa-Duarte, M Giesig, and L. MLiz-Marzan, Stabilization of CdS semiconductor nanoparticles againstphotodegradation by a silica coating procedure, Chem. Phys. Lett., 1998,286: 497, the entire contents of which is explicitly incorporated hereinby reference in its entirety), citrate-stabilized CdTe:Mn 2+/SiO₂nanocrystals suitable for the invention described here can be preparedwith a silica coating:

-   -   (1) To a CdTe:Mn 2+ nanoparticle solution (50 ml), a freshly        prepared aqueous solution of 3-(mercaptopropyl)trimethoxysilane        (MPS) (0.5 ml, 1 mM) (Sigma) is added under vigorous stirring.        The function of MPS is that its mercapto group can directly bond        to the surface Cd sites of CdTe, while leaving the silane groups        pointing toward solution from where silicate ions approach the        particle surface; (2) Addition of 2 ml of sodium silicate (Alfa)        solution at pH of 10.5 under vigorous stirring; (3) The        resulting dispersion (pH ˜8.5) is allowed to stand for 5 days,        so that silica slowly polymerizes onto the particle surface;        and (4) Transfer of the dispersion to ethanol so that the excess        dissolved silicate can precipitate out, increasing the silica        shell thickness.

Alternatively, as shown in FIG. 3C and FIG. 3D, luminescing particles inencapsulated structures 10 could be placed in the vicinity of themedium. In one embodiment for the invention described here, luminescingparticles are coated on the interior of quartz or glass tubes 9 andsealed. In another embodiment, luminescing particles could be coated onthe surface of spheres or tubes, and afterwards encapsulated with silica(or other suitable passivation layer) using a vapor deposition orsputtering process or spin-on glass process of the solution processdescribed above to make the encapsulation structures 10 which may bepart of re-entrant structures extending from walls of a container (as inFIG. 3C) or which may be part of a fluidized bed structure (as in FIG.3D).

In the either configuration, the medium to be treated would flow by theencapsulated structures 10, or flow along with encapsulated structures6, and the separation distance between the encapsulated structures 6, 10would be set a distance smaller than the UV penetration depth in themedium.

A suitable light source (such as one of the x-ray sources discussedabove) can be used to stimulate the luminescing particles in theencapsulated structures 10. In one embodiment of the invention describedhere, the concentration of luminescing particles in the medium or thespacing between the encapsulated structures 10 is set such thatluminescing particles are separated from each other in the medium byless than a UV depth of penetration into the medium. Higherconcentrations are certainly usable and will generate higher UV fluxesshould the energy source have enough intensity to “light” all theluminescing particles.

For a relatively unclouded aqueous medium, solar UV-B irradiancedecreases to 1% after penetration into the water samples between 0.2 mand 1 m, whereas UV-A penetrates on the order of several meters. Forsuch mediums, the concentration of luminescing particles is moredetermined by the time needed for the intended UV flux to producedeactivation or activation of an agent in the medium, rather than havingto be set based on a concentration of luminescent particles where themedium itself does not occlude the UV stimulated emission frompenetrating throughout the medium. The placement of the luminescentparticles in the medium and in the vicinity of the medium is notrestricted by the optical density of the medium.

Based on published data of an average of 5.2 spontaneous photons emittedfrom BaFBr:Eu²⁺ for every keV of X-ray absorbed (M. Thorns, H vonSeggern, Method for the determination of photostimulable defect centerconcentrations, production rates, and effective formation energies, J.Appl. Phys. 1994, 75: 4658-4661, the entire contents of which is hereinexplicitly incorporated by reference in its entirety.), one expects thatabout 50 photons are emitted from a CdTe nanoparticle for each 50 keVX-ray absorbed.

Based on the results in U.S. Pat. Appl. Publ. No. 2007/0063154 for X-rayspectra of CdTe/BaFBr:Eu²⁺ nanocomposites prepared using a concentrationof 0.8 ml L-cysteine stabilized CdTe particle solution in 0.2 gBaFBr:Eu²⁺ phosphor. As the X-ray irradiation time increases, the X-rayluminescence intensity of Eu²⁺ at 390 nm increases in intensity. Thisphenomenon has been discussed in W. Chen, S. P. Wang, S. Westcott, J.Zhang, A. G. Joly, and D. E. McCready, Structure and luminescence ofBaFBr:Eu ²⁺ and BaFBr:Eu ²⁺ , Tb ³⁺ phosphors and thin films, J. Appl.Phys. 2005, 97: 083506, the entire contents of these references areherein incorporated by reference in their entirety.

Hence, in one embodiment of the invention, a minimum baselineconcentration of about 10⁹ nanoparticles per cm³ for 200 nm diameterparticles is expected to be sufficient for UV emission to produce achange in the medium. The invention is not limited to this concentrationrange, but rather this range is given as an illustrative example.Indeed, higher concentrations will increase the UV emission per unittime and provide faster reactions, which in general would be consideredmore useful in industrial applications where product throughput is aconcern.

Sterilization and Cold Pasteurization of Fluids

Table 1 included below shows appropriate intensities for germicidaldestruction.

TABLE 1 Germicidal energies needed to destroy Approximate intensity(μW/cm²) required for 99% destruction of microorganisms: Bacteria  10400 Protozoa (single celled organism) 105 000 Paramecium (slipper shaped200 000 protozoa) Chlorella (unicellular fresh-water  13 000 alga)Flagellate(protozoan or alga with  22 000 flagella) Sporozoan (parasiticprotozoans) 100 000 Virus  8 000

Accordingly, the energy modulation agents (or luminescing particles) ofthe invention (as discussed above with regard to FIGS. 3B and 3C) can beprovided on the interior of sealed quartz or glass tubes or can beprovided coated on the surface of spheres or tubes, and furtherencapsulated with a silica or passivation layer. In either configurationfor the invention described here, a medium could flow by theencapsulated structures 6, 10 with a separation distance between theencapsulated structures or the quartz or glass tubes being made smallerthan the UV penetration depth.

For example, it is known that ultraviolet (UV) with a wavelength of 254nm tends to inactivate most types of microorganisms. Most juices areopaque to UV due to the high-suspended solids in them and hence theconventional UV treatment, usually used for water treatment, cannot beused for treating juices. In order to make the process efficient, a thinfilm reactor constructed from glass has been used with the juice flowingalong the inner surface of a vertical glass tube as a thin film. See“Ultraviolet Treatment of Orange Juice” by Tran et al. published inInnovative Food Science & Emerging Technologies (Volume 5, Issue 4,December 2004, Pages 495-502), the entire contents of which areincorporated herein by reference. Tran et al. reported therein decimalreduction doses required for the reconstitute orange juices (OJ; 10.5°Brix) were 87±7 and 119±17 mJ/cm² for the standard aerobic plate count(APC) and yeast and moulds, respectively. In that article, the shelflife of fresh squeezed orange juice was extended to 5 days with alimited exposure of UV (73.8 mJ/cm²). The effect of UV on theconcentration of Vitamin C was investigated using both HPLC andtitration methods of measurements. The degradation of Vitamin C was 17%under high UV exposure of 100 mJ/cm², which was similar to that usuallyfound in thermal sterilization. Enzyme pectin methylesterase (PME)activity, which is the major cause of cloud loss of juices, was alsomeasured. The energy required for UV treatment of orange juice (2.0 kWh/m³) was much smaller than that required in thermal treatment (82 kWh/m³). The color and pH of the juice were not significantly influencedby the treatment.

The invention described herein offers advantages over this approach inthat the energy modulation agents can be placed inside fixtures such asquartz or glass (encapsulation structures 8) within the orange juice (orother fluid medium) and irradiated with x-rays (or other penetratingradiation) through for example a plastic or aluminum container 9 toactivate the energy modulation agents 3 and 6 in the orange juice. Assuch, the expense and fragility of a thin film reactor constructed fromglass of other similar structure is avoided.

While discussed with regard to orange juice, any other medium to besterilized including food products, medical products and cosmeticproducts could be treated using the technique of the invention describedherein.

Sterilization of Medical and Pharmaceutical Articles

As noted above, medical bottle caps need to be sterilized between thebase cap material and the seal material which contacts to the base ofthe medical bottle. Steam autoclaves are insufficient for this purposeas once glued, the steam is unable to penetrate into the glue seam.

Gamma irradiation has been used conventionally to sterilize medicalbottle caps and other medical, pharmaceutical, and cosmetic articlessuch as surgical disposables (e.g., surgical bandages, dressings, gaugepads, nappies, delivery kits, and etc.), metallic products (e.g.,surgical blades, implants, aluminum caps, containers, etc.), and plasticand rubber Items (e.g., petri-dish, centrifuge tube, blood collectionsets, scalp vein sets, shunt valves, rubber gloves, contraceptivedevices, gowns, wraps covers, sheets, etc.). The invention would beapplicable for the sterilization of any “interior” surfaces of these andother products.

In one embodiment of the invention described herein, UV luminescentparticles would be included in an adhesive layer when the seal materialis applied to the bottle cap. X-ray irradiation would then be capable ofcuring the adhesive (if for example the adhesive were a photosensitiveadhesive as discussed below in greater detail) and would produce withinthe adhesive medium UV radiation for direct sterilization or for theproduction of singlet oxygen or ozone for biological germicide.

While illustrated here with regard to medical bottle caps, otheradhesively constructed devices could benefit from these procedures inwhich the adhesive medium is cured and/or sterilized during activationof energy modulation agents 3 and 6.

Sterilization of Blood Products

U.S. Pat. No. 6,087,141 (the entire contents of which are incorporatedherein by reference) describes an ultraviolet light actived psoralenprocess for sterilization of blood transfusion products. Here, theinvention can be applied for example in the equipment shown in FIGS. 3Cand 3D for the treatment of or the neutralization of AIDS and HIV orother viral or pathogenic agents in blood transfusion products. In thisembodiment, at least one photoactivatable agent is selected frompsoralens, pyrene cholesteryloleate, acridine, porphyrin, fluorescein,rhodamine, 16-diazorcortisone, ethidium, transition metal complexes ofbleomycin, transition metal complexes of deglycobleomycin organoplatinumcomplexes, alloxazines, vitamin Ks, vitamin L, vitamin metabolites,vitamin precursors, naphthoquinones, naphthalenes, naphthols andderivatives thereof having planar molecular conformations,porphorinporphyrins, dyes and phenothiazine derivatives, coumarins,quinolones, quinones, and anthroquinones. These photoactivatable agentsare introduced into the blood product (or a patient's blood stream). Apenetrating energy is applied to the blood product (or to the patient).The energy modulation agents (either included in the blood product) orin encapsulated structures 10 generate secondary light such as UV lightwhich activates the photoactivatable agents in the blood products.

In a specific example, the photoactivatable agent is a psoralen, acoumarin, or a derivative thereof, and as discussed above, one cansterilize blood products in vivo (i.e., in a patient) or in a containerof the blood product (such as for example donated blood). The treatmentcan be applied to treat disorders such as for example a cancer cell, atumor cell, an autoimmune deficiency symptom virus, or a blood-bornegermicide is treated by the psoralen, the coumarin, or the derivativethereof.

Waste Water Detoxification

Photocatalysis has also been used as tertiary treatment for wastewaterto comply with the regulatory discharge limits and to oxidize persistentcompounds that have not been oxidized in the biological treatment.Photocatalysis has being applied to the elimination of severalpollutants (e.g., alkanes, alkenes, phenols, aromatics, pesticides) withgreat success.

In many cases, total mineralization of the organic compounds has beenobserved. Several photocatalysts, such as CdS, Fe₂O₃, ZnO, WO₃, and ZnS,have been studied, but the best results have been achieved with TiO₂P₂₅.These photocatalyst are usable for the invention described here.

The wastewaters of an oil refinery are the waters resulting from washingthe equipment used in the process, undesirable wastes, and sanitarysewage. These effluents have high oil and grease contents, besides otherorganic compounds in solution. These pollutants form a residual chemicaloxygen demand (COD) that may pose serious toxic hazards to theenvironment.

It is known that photocatalysis can be used for waste water reductionremediation. U.S. Pat. No. 5,118,422 (the entire contents of which areincorporated herein by reference) to Cooper et al. describe anultraviolet driven photocatalytic post-treatment technique for purifyinga water feedstock containing an oxidizable contaminant compound. In thiswork, the water feedstock was mixed with photocatalytic semiconductorparticles (e.g., TiO₂, ZnO, CdS, CdSe, Sn0₂, SrTiO₃, WO₃, Fe₂O₃, andTa₂O₅ particles) having a particle size in the range of about 0.01 toabout 1.0 micron and in an amount of between about 0.01% and about 0.2%by weight of the water. The water including the semiconductor mixture isexposed to band-gap photons for a time sufficient to effect an oxidationof the oxidizable contaminant to purify the water. Crossflow membranefiltration was used to separate the purified water from thesemiconductor particles. Cooper et al. show that the organic impuritycarbon content of simulated reclamation waters at nominal 40 PPM levelwere reduced to parts per billion using a recirculation batch reactor.

Cooper et al. identified that one important aspect of the photocatalyticprocess is the adsorption of the organic molecules onto the extremelylarge surface area presented by the finely divided powders dispersed inthe water. Cooper et al. further indicated that, in photoelectrochemicalapplications, advantage is taken of the fact that the solid phase (ametal oxide semiconductor) is also photo-active and that the generatedcharge carriers are directly involved in the organic oxidation. Theadsorption of the band-gap photon by the semiconductor particle resultsin the formation of an electron (e⁻)/hole(h⁺) pair. Cooper et al.explain that the electrons generated in the conduction band react withsolution oxygen forming the dioxygen anion (O²⁻) species whichsubsequently undergo further reactions resulting in the production ofthe powerfully oxidizing hydroxyl radical species, OH. These powerfuloxidants are known to oxidize organic compounds by themselves.Additionally, Cooper et al. explain that the strongly oxidizing holesgenerated in the valence band have sufficient energy to oxidize allorganic bonds.

In the reactor of Cooper et al., turbulence is necessary in order toensure that the waste water contaminants and the photocatalytic titaniaparticles are exposed to the UV light. Cooper et al. explain that themost basic considerations of photocatalyst light adsorption and itsrelationship to convective mixing. For a 0.1 wt % photocatalyst loading,experiments have shown that 90% of the light is absorbed within 0.08 cm.This is primarily due to the large UV absorption coefficient of thephotocatalyst and therefore, most of the photoelectrochemistry occurswithin this illuminated region. By operating the reactor of Cooper etal. with a Reynolds number (Re) of 4000, a significant portion of thephotoactive region is ensured of being within the well mixed turbulentzone.

Santos et al. have reported in “Photocatalysis as a tertiary treatmentfor petroleum refinery wastewaters” published in Braz. J. Chem. Eng.vol. 23, No. 4, 2006 (the entire contents of which are incorporatedherein by reference), photocatalysis for tertiary treatment forpetroleum refinery wastewaters which satisfactorily reduced the amountof pollutants to the level of the regulatory discharge limits andoxidized persistent compounds that had not been oxidized in thebiological treatment. The treatment sequence used by the refinery(REDUC/PETROBRAS, a Brazilian oil refinery) is oil/water separationfollowed by a biological treatment. Although the process efficiency interms of biological oxygen demand (BOD) removal is high, a residual andpersistent COD and a phenol content remains. The refining capacity ofthe refinery is 41,000 m³/day, generating 1,100 m³/h of wastewater,which are discharged directly into the Guanabara Bay (Rio de Janeiro).Treating the residual and persistent COD remains a priority.

Santos et al. conducted a first set of experiments carried out in anopen 250 mL reactor containing 60 mL of wastewater. In the second set ofexperiments, a Pyrex® annular reactor containing 550 mL of wastewaterwas used (De Paoli and Rodrigues, 1978), as shown in FIG. 1. Thereaction mixtures inside the reactors were maintained in suspension bymagnetic stirring. In all experiments, air was continuously bubbledthrough the suspensions. A 250 W Phillips HPL-N medium pressure mercuryvapor lamp (with its outer bulb removed) was used as the UV-light source(radiant flux of 108 J·m⁻²·s⁻¹ at 8>254 nm). In one set of experiments,the lamp was positioned above the surface of the liquid at a fixedheight (12 cm). In the second set, the lamp was inserted into the well.All experiments by Santos et al. were performed at 25±1° C. The catalystconcentration ranged from 0.5 to 5.5 g L⁻¹ and the initial pH rangedfrom 3.5 to 9.

In the invention described herein, luminescing particles or other energymodulation agents would be placed inside quartz or glass fixtures withinthe waste water or would be placed on silica encapsulated structureswithin the waste water which, like the photocatalytic TiO₂, could beentrained in the waste water during the irradiation.

Upon irradiation with x-rays (or other penetrating radiation) throughfor example a plastic or aluminum container, activation of theluminescing particles (i.e., energy modulation agents) would generate UVlight in nearby presence of the photocatalytic agent. In other words forthe invention described herein, the luminescent particles or otherenergy modulation agents are mixed along with the photocatalyticsemiconductor particles in the waste water fluid stream, and theexterior activation energy source penetrates the container (e.g., aplastic or aluminum container) and irradiates the bulk of the wastewater, producing UV light throughout the waste water which in turndrives the photocatalytic reactions.

As such, the invention described herein offers a number to advantagesover that described above, including the elimination of expensiveholding tanks for the waste water, the avoidance of having to pump thewastewater at higher pressures or flowrates to produce sufficientturbulence, and the generation of UV light throughout the wastewater tothereby provide faster bulk processing of the waste water.

Photostimulation

Photostimulation is a field in which light is applied to in order toalter or change a physical property. For example, there has been anincreased focus on the use of biodegradable polymers in consumer andbiomedical fields. Polylactic acid (PLA) plastics andpolyhydroxyalkanoates (PHA) plastics have been playing a vital role infulfilling the objectives. But their relatively hydrophobic surfaceslimit their use in various applications. Hence, there is a need tosurface modify these film surfaces. Due to the lack of any modifiableside chain groups, workers have used a sequential two step photograftingtechnique for the surface modification of these biopolymers. In stepone, benzophenone was photografted on the film surface and in step two,hydrophilic monomers like acrylic acid and acrylamide werephotopolymerized from the film surfaces.

Workers have found that UV irradiation could realize an effective graftcopolymerization. UV-assisted photografting in ethanol has been used togrow hydrophilic polymers (e.g., poly(acrylic acid) and polyacrylamide)from the surfaces of PLA, PHA, and PLA/PHA blend films. In that work, afunctional polyurethane (PU) surface was prepared by photo-graftingN,N-dimethylaminoethyl methacrylate (DMAEM) onto the membrane surface.Grafting copolymerization was conducted by the combined use of thephoto-oxidation and irradiation grafting. PU membrane was photo-oxidizedto introduce the hydroperoxide groups onto the surface, then themembrane previously immersed in monomer solution was irradiated by UVlight. Results have shown prior to the invention that UV irradiation canrealize graft copolymerization effectively.

In the invention described herein, these processes are expedited by theinclusion of luminescing particles or other energy modulation agents indispersion in the fluid medium being used for photostimulation.

Upon irradiation with x-rays (or other penetrating radiation) throughfor example a plastic or aluminum container, activation of theluminescing particles (i.e., energy modulation agents) would generate UVlight throughout the volume of the medium (eliminating any shadowingeffects) and permitting batch or bulk type processing to occur inparallel throughout the container.

In other examples, the interior generation of light inside a bulk mediummay serve to stimulate a chemical or biological process either by directinteraction of the light with activatable agents in the medium or theindirect generation of heat which the invention described here by way ofdispersed energy modulation agents would provide a controlled anduniform way to heat a vat of material in a biological or chemicalprocess.

Photodeactivation

In many industrial processes, especially food and beverage industries,yeasts are used to produce changes in a medium such as the conversion ofsugars in the raw product. One particularly prominent example is in thewine industry. Stopping the wine from fermenting any further wouldpreserve the current level of sweetness. Likewise, allowing the wine tocontinue fermenting further would only make the wine less sweet witheach passing day. Eventually the wine would become completely dry atwhich time the fermentation would stop on its own. This is becauseduring the fermentation process yeast turns the sugar into alcohol.

Wanting to stop a fermentation is all good in and of itself. Butunfortunately, there is really no practical way to successfully stop afermentation dead in its tracks. Additives such as sulphite and sorbatecan be added to stabilize a fermented product and stop additionalfermentation. Many winemakers will turn to sulfites such as that foundin Sodium Bisulfite or Campden tablets for the answer. But, these twoitems are not capable of reliably killing enough of the yeast toguarantee a complete stop of the activity—at least not at normal dosesthat leave the wine still drinkable.

Once the bulk of the sulfites from either of these ingredients dissipatefrom the wine into the air—as sulfites do—there is a very strong chancethat the remaining few live yeast cells will start multiplying andfermenting again if given enough time. This usually happens at a mostinconvenient time, like after the wine has been bottled and stowed away.

Potassium sorbate is another ingredient that many winemakers considerwhen trying to stop a wine from fermenting any further. There is a lotof misunderstanding surrounding this product. It is typically called forby home wine making books when sweetening a wine. This is a situationwhere the fermentation has already completed and is ready for bottling.One adds the potassium sorbate along with the sugar that is added forsweetening.

The potassium sorbate stops the yeast from fermenting the newly addedsugar. So, many winemakers assume potassium sorbate can stop an activefermentation as well, but, potassium sorbate does not kill the yeast atall, but rather it makes the yeast sterile. In other words, it impairsthe yeast's ability to reproduce itself. But, it does not hinder theyeast's ability to ferment sugar into alcohol.

Ultraviolet light is known to destroy yeast cultures, but has restrictedapplications due to the inability of UV light to penetrate throughoutthe fluid medium. While heat can be used to destroy the yeast activity,cooking of the product may be premature or may produce undesirablechanges in the consistency and taste. For liquid or fluid food products,the same techniques described above for liquid pasteurization could beused for the invention described here. For non-liquid products, energymodulation agents with little and preferably no toxicity (e.g. Fe oxidesor titanium oxides) could be added. Here, the concentration of theseadditives would likely be limited by any unexpected changes in taste.

Photoactivated Cross-linking and Curing of Polymers

In this application, luminescing particles (or energy modulation agents)are provided and distributed into an uncured polymer based medium forthe activation of photosensitive agents in the medium to promotecross-linking and curing of the polymer based medium.

As noted above, for adhesive and surface coating applications, lightactivated processing is limited due to the penetration depth of UV lightinto the processed medium. In light activated adhesive and surfacecoating processing, the primary limitation is that the material to becured must see the light—both in type (wavelength or spectraldistribution) and intensity. This limitation has meant that one mediumtypically has to transmit the appropriate light. In adhesive and surfacecoating applications, any “shaded” area will require a secondary curemechanism, increasing cure time over the non-shaded areas and furtherdelaying cure time due to the existent of a sealed skin through whichsubsequent curing must proceed.

Conventionally, moisture-curing mechanisms, heat-curing mechanisms, andphoto-initiated curing mechanisms are used to initiate cure, i.e.,cross-linking, of reactive compositions, such as reactive silicones,polymers, and adhesives. These mechanisms are based on eithercondensation reactions, whereby moisture hydrolyzes certain groups, oraddition reactions that can be initiated by a form of energy, such aselectromagnetic radiation or heat.

The invention described herein can use any of the following lightactivated curing polymers as well as others known in the art to whichthe luminescing particles (or energy modulation agents) are added.

For example, one suitable light activated polymer compound includes UVcuring silicones having methacrylate functional groups. U.S. Pat. No.4,675,346 to Lin, the disclosure of which is hereby expresslyincorporated herein by reference, is directed to UV curable siliconecompositions including at least 50% of a specific type of siliconeresin, at least 10% of a fumed silica filler and a photoinitiator, andcured compositions thereof. Other known UV curing silicone compositionssuitable for the invention include organopolysiloxane containing a(meth)acrylate functional group, a photosensitizer, and a solvent, whichcures to a hard film. Other known UV curing silicone compositionssuitable for the invention include compositions of an organopolysiloxanehaving an average of at least one acryloxy and/or methacryloxy group permolecule; a low molecular weight polyacrylyl crosslinking agent; and aphotosensitizer.

Loctite Corporation has designed and developed UV and UV/moisture dualcurable silicone compositions, which also demonstrate high resistance toflammability and combustibility, where the flame-retardant component isa combination of hydrated alumina and a member selected from the groupconsisting of organo ligand complexes of transition metals,organosiloxane ligand complexes of transition metals, and combinationsthereof. See U.S. Pat. Nos. 6,281,261 and 6,323,253 to Bennington. Theseformulations are also suitable for the invention.

Other known UV photoactivatable silicones include siliconesfunctionalized with for example carboxylate, maleate, cinnamate andcombinations thereof. These formulations are also suitable for theinvention. Other known UV photoactivatable silicones suitable for theinvention include benzoin ethers (“UV free radical generator”) and afree-radical polymerizable functional silicone polymers, as described inU.S. Pat. No. 6,051,625 whose content is incorporated herein byreference in its entirety. The UV free radical generator (i.e., thebenzoin ether) is contained at from 0.001 to 10 wt % based on the totalweight of the curable composition. Free radicals produced by irradiatingthe composition function as initiators of the polymerization reaction,and the free radical generator can be added in a catalytic quantityrelative to the polymerizable functionality in the subject composition.Further included in these silione resins can be silicon-bonded divalentoxygen atom compounds which can form a siloxane bond while the remainingoxygen in each case can be bonded to another silicon to form a siloxanebond, or can be bonded to methyl or ethyl to form an alkoxy group, orcan be bonded to hydrogen to form silanol. Such compounds can includetrimethylsilyl, dimethylsilyl, phenyldimethylsilyl, vinyldimethylsilyl,trifluoropropyldimethylsilyl, (4-vinylphenyl)dimethylsilyl,(vinylbenzyl)dimethylsilyl, and (vinylphenethyl)dimethylsilyl.

The photoinitiator component of the invention is not limited to thosefree radical generators given above, but may be any photoinitiator knownin the art, including the afore-mentioned benzoin and substitutedbenzoins (such as alkyl ester substituted benzoins), Michler's ketone,dialkoxyacetophenones, such as diethoxyacetophenone (“DEAP”),benzophenone and substituted benzophenones, acetophenone and substitutedacetophenones, and xanthone and substituted xanthones. Other desirablephotoinitiators include DEAP, benzoin methyl ether, benzoin ethyl ether,benzoin isopropyl ether, diethoxyxanthone, chloro-thio-xanthone,azo-bisisobutyronitrile, N-methyl diethanolaminebenzophenone, andmixtures thereof. Visible light initiators include camphoquinone,peroxyester initiators and non-fluorene-carboxylic acid peroxyesters.

Commercially available examples of photoinitiators suitable for theinvention include those from Vantico, Inc., Brewster, N.Y. under theIRGACURE and DAROCUR tradenames, specifically IRGACURE 184(1-hydroxycyclohexyl phenyl ketone), 907(2-methyl-1-[4-(methylthio)phenyl]-2-morpholino propan-1-one), 369(2-benzyl-2-N,N-dimethylamino-1-(4-morpholinophenyl)-1-butanone), 500(the combination of 1-hydroxy cyclohexyl phenyl ketone andbenzophenone), 651 (2,2-dimethoxy-2-phenyl acetophenone), 1700 (thecombination of bis(2,6-dimethoxybenzoyl-2,4,4-trimethyl pentyl)phosphineoxide and 2-hydroxy-2-methyl-1-phenyl-propan-1-one), and 819[bis(2,4,6-trimethyl benzoyl)phenyl phosphine oxide] and DAROCUR 1173(2-hydroxy-2-methyl-1-phenyl-1-propane) and 4265 (the combination of2,4,6-trimethylbenzoyldiphenyl-phosphine oxide and2-hydroxy-2-methyl-1-phenyl-propan-1-one); and IRGACURE 784DC(bis(.eta..sup.5-2,4-cyclopentadien-1-yl)-bis[2,6-difluoro-3-(1H-pyrrol-1-yl)phenyl]titanium).

Generally, the amount of photoinitiator (or free radical generators)should be in the range of about 0.1% to about 10% by weight, such asabout 2 to about 6% by weight. The free radical generator concentrationfor benzoin ether is generally from 0.01 to 5% based on the total weightof the curable composition.

A moisture cure catalyst can also be included in an amount effective tocure the composition. For example, from about 0.1 to about 5% by weight,such as about 0.25 to about 2.5% by weight, of the moisture curecatalyst can be used in the invention to facilitate the cure processbeyond that of photo-activated curing. Examples of such catalystsinclude organic compounds of titanium, tin, zirconium and combinationsthereof. Tetraisopropoxytitanate and tetrabutoxytitanate are suitable asmoisture cure catalyst. See also U.S. Pat. No. 4,111,890, the disclosureof which is expressly incorporated herein by reference.

Included in the conventional silicone composition (and other inorganicand organic adhesive polymers) suitable for the invention are variousinorganic fillers. For example, hollow microspheres supplied by Kishunder the trade name Q-CEL are free flowing powders, white in color.Generally, these borosilicate hollow microspheres are promoted asextenders in reactive resin systems, ordinarily to replace heavyfillers, such as calcium carbonate, thereby lowering the weight ofcomposite materials formed therewith. Q-CEL 5019 hollow microspheres areconstructed of a borosilicate, with a liquid displacement density of0.19 g/cm², a mean particle size of 70 microns, and a particle sizerange of 10-150 urn. Other Q-CEL products are shown below in tabularform. Another commercially available hollow glass microsphere is sold byKish under the trade name SPHERICEL. SPHEREICEL 110P8 has a meanparticle size of about 11.7 microns, and a crush strength of greaterthan 10,000 psi. Yet other commercially available hollow glassmicrosphere are sold by the Schundler Company, Metuchen, N.J. under thePERLITE tradename, Whitehouse Scientific Ltd., Chester, UK and 3M,Minneapolis, Minn. under the SCOTCHLITE tradename.

In general, these inorganic filler components (and others such as fumedsilica) add structural properties to the cured composition, as well asconfers flowability properties to the composition in the uncured stateand increase the transmissivity for the UV cure radiation. When present,the fumed silica can be used at a level of up to about 50 weightpercent, with a range of about 4 to at least about 10 weight percent,being desirable. While the precise level of silica may vary depending onthe characteristics of the particular silica and the desired propertiesof the composition and the reaction product thereof, care should beexercised by those persons of ordinary skill in the art to allow for anappropriate level of transmissivity of the inventive compositions topermit a UV cure to occur.

Desirable hydrophobic silicas include hexamethyldisilazane-treatedsilicas, such as those commercially available from Wacker-Chemie,Adrian, Mich. under the trade designation HDK-2000. Others includepolydimethylsiloxane-treated silicas, such as those commerciallyavailable from Cabot Corporation under the trade designation CAB—O-SILN70-TS, or Degussa Corporation under the trade designation AEROSIL 8202.Still other silicas include trialkoxyalkyl silane-treated silicas, suchas the trimethoxyoctyl silane-treated silica commercially available fromDegussa under the trade designation AEROSIL R805; and 3-dimethyldichlorosilane-treated silicas commercially available from Degussa underthe trade designation R972, R974 and R976.

While these inorganic fillers have extended the use of conventional UVcured silicone systems to permit the curing of materials beyond a skindepth of UV penetration, these inorganic fillers alone do not overcomeshadowing effects and suffer from UV scattering which effectively makesfor a smaller penetration depth. In the invention described herein, theinclusion of these inorganic fillers along with luminescing particlesprovide a mechanism by which uniform light activated cures can occurdeep inside of the body of adhesive-solidified assemblies in regionsthat would normally be shadowed or not with the reach of external UV orother light sources.

Accordingly, in this example of the invention described herein,conventional silicone and polymeric adhesive or release or coatingcompositions are prepared using conventional mixing, heating, andincubation techniques. Included in these conventional compositions areluminescing particles. These luminescing particle containingcompositions can then be applied to surfaces of objects to be fixedtogether or to surfaces where a hard coating is desired or cast in acurable form for the production of molded objects. The luminescingparticles in these compositions upon activation will produce radiantlight for photoactivated cure of the luminescing particle containingpolymer composition. The density of luminescing particles in thesecompositions will depend on the “light transparency” of the luminescingparticle containing composition. Where these compositions contain asignificant amount of the inorganic filler as discussed above, theconcentration of luminescing particles can be reduced for example ascompared to a composition with a black color pigment where the lighttransparency will be significantly reduced.

One advantage of the invention described here as seen from this exampleis that now color pigments can be included in the light curable resinswithout significant compromise in the cured product performance. Thesecolor pigments may include one or more colored pigments well known tothose of ordinary skill in the art. Such pigments are generally metaloxides and include, but are not limited to, titanium dioxide, ironoxides, organic complexes, mica, talc and quartz. One pigment may beused, or a combination of two or more pigments may be utilized.Different colors can be obtained by choosing proper pigments andcombining them in a similar fashion as set forth in the followingexamples with the necessary adjustments, common in the paint industry,being made. Accordingly, in one embodiment of the invention, these colorpigments including carbon black may also be included as an opticallyopaque materials to limit the propagation of internally generated lightfrom the point of generation.

U.S. Pat. No. 7,294,656 to Bach et al., the entire disclosure of whichis incorporated herein by reference, describes a non-aqueous compositioncurable by UV radiation broadly containing a mixture of two UV curableurethane acrylates that have several advantages over conventionalradiation-curable compositions. The Bache et al. compositions can becured in a relatively short time using UV-C (200-280 nm), UV-B (280-320nm), UV-A (320-400 nm) and visible (400 nm and above) radiation. Inparticular, Bache et al. compositions can be cured using radiationhaving a wavelength of 320 nm or more. When fully cured (regardless ofthe type of radiation used), the Bach et al. compositions exhibithardnesses and impact resistances at least comparable to conventionalcoatings.

In the invention described here, the luminescing particles (or energymodulation agents) described above are added to these Bach et al.compositions, optionally including in one embodiment various colorpigments. Due to the fact that the exterior energy source penetratesthroughout the entirety of the Bach et al. compositions, thicker surfacecoatings can be realized. Further, the coatings can be applied tointricate surfaces having for example been prepared with recesses orprotrusions. Curing with the recesses and around the protrusions withoutbeing limited by conventional UV shading will likely provide enhancedadherence of the surface coating to the work piece.

Computer-Assisted Control

In one embodiment of the invention, there is provided a computerimplemented system for designing and selecting suitable combinations ofinitiation energy source, energy modulation agent, and activatableagent. For example, the computer system 5 can include a centralprocessing unit (CPU) having a storage medium on which is provided: adatabase of excitable compounds, a first computation module for aphotoactivatable agent or energy transfer agent, and a secondcomputation module predicting the requisite energy flux needed tosufficiently activate the or energy transfer agent or photoactivatableagent.

FIG. 4 illustrates a computer system 1201 for implementing variousembodiments of the invention. The computer system 1201 may be used asthe computer system 5 to perform any or all of the functions describedabove. The computer system 1201 includes a bus 1202 or othercommunication mechanism for communicating information, and a processor1203 coupled with the bus 1202 for processing the information. Thecomputer system 1201 also includes a main memory 1204, such as a randomaccess memory (RAM) or other dynamic storage device (e.g., dynamic RAM(DRAM), static RAM (SRAM), and synchronous DRAM (SDRAM)), coupled to thebus 1202 for storing information and instructions to be executed byprocessor 1203. In addition, the main memory 1204 may be used forstoring temporary variables or other intermediate information during theexecution of instructions by the processor 1203. The computer system1201 further includes a read only memory (ROM) 1205 or other staticstorage device (e.g., programmable read only memory (PROM), erasablePROM (EPROM), and electrically erasable PROM (EEPROM)) coupled to thebus 1202 for storing static information and instructions for theprocessor 1203.

The computer system 1201 also includes a disk controller 1206 coupled tothe bus 1202 to control one or more storage devices for storinginformation and instructions, such as a magnetic hard disk 1207, and aremovable media drive 1208 (e.g., floppy disk drive, read-only compactdisc drive, read/write compact disc drive, compact disc jukebox, tapedrive, and removable magneto-optical drive). The storage devices may beadded to the computer system 1201 using an appropriate device interface(e.g., small computer system interface (SCSI), integrated deviceelectronics (IDE), enhanced-IDE (E-IDE), direct memory access (DMA), orultra-DMA).

The computer system 1201 may also include special purpose logic devices(e.g., application specific integrated circuits (ASICs)) or configurablelogic devices (e.g., simple programmable logic devices (SPLDs), complexprogrammable logic devices (CPLDs), and field programmable gate arrays(FPGAs)).

The computer system 1201 may also include a display controller 1209coupled to the bus 1202 to control a display, such as a cathode ray tube(CRT), for displaying information to a computer user. The computersystem includes input devices, such as a keyboard and a pointing device,for interacting with a computer user and providing information to theprocessor 1203. The pointing device, for example, may be a mouse, atrackball, or a pointing stick for communicating direction informationand command selections to the processor 1203 and for controlling cursormovement on the display. In addition, a printer may provide printedlistings of data stored and/or generated by the computer system 1201.

The computer system 1201 performs a portion or all of the processingsteps of the invention (such as for example those described in relationto FIG. 5) in response to the processor 1203 executing one or moresequences of one or more instructions contained in a memory, such as themain memory 1204. Such instructions may be read into the main memory1204 from another computer readable medium, such as a hard disk 1207 ora removable media drive 1208. One or more processors in amulti-processing arrangement may also be employed to execute thesequences of instructions contained in main memory 1204. In alternativeembodiments, hard-wired circuitry may be used in place of or incombination with software instructions. Thus, embodiments are notlimited to any specific combination of hardware circuitry and software.

As stated above, the computer system 1201 includes at least one computerreadable medium or memory for holding instructions programmed accordingto the teachings of the invention and for containing data structures,tables, records, or other data described herein. Examples of computerreadable media are compact discs, hard disks, floppy disks, tape,magneto-optical disks, PROMs (EPROM, EEPROM, flash EPROM), DRAM, SRAM,SDRAM, or any other magnetic medium, compact discs (e.g., CD-ROM), orany other optical medium, punch cards, paper tape, or other physicalmedium with patterns of holes, a carrier wave (described below), or anyother medium from which a computer can read.

Stored on any one or on a combination of computer readable media, theinvention includes software for controlling the computer system 1201,for driving a device or devices for implementing the invention, and forenabling the computer system 1201 to interact with a human user. Suchsoftware may include, but is not limited to, device drivers, operatingsystems, development tools, and applications software. Such computerreadable media further includes the computer program product of theinvention for performing all or a portion (if processing is distributed)of the processing performed in implementing the invention.

The computer code devices of the invention may be any interpretable orexecutable code mechanism, including but not limited to scripts,interpretable programs, dynamic link libraries (DLLs), Java classes, andcomplete executable programs. Moreover, parts of the processing of theinvention may be distributed for better performance, reliability, and/orcost.

The term “computer readable medium” as used herein refers to any mediumthat participates in providing instructions to the processor 1203 forexecution. A computer readable medium may take many forms, including butnot limited to, non-volatile media, volatile media, and transmissionmedia. Non-volatile media includes, for example, optical, magneticdisks, and magneto-optical disks, such as the hard disk 1207 or theremovable media drive 1208. Volatile media includes dynamic memory, suchas the main memory 1204. Transmission media includes coaxial cables,copper wire and fiber optics, including the wires that make up the bus1202. Transmission media also may also take the form of acoustic orlight waves, such as those generated during radio wave and infrared datacommunications.

Various forms of computer readable media may be involved in carrying outone or more sequences of one or more instructions to processor 1203 forexecution. For example, the instructions may initially be carried on amagnetic disk of a remote computer. The remote computer can load theinstructions for implementing all or a portion of the invention remotelyinto a dynamic memory and send the instructions over a telephone lineusing a modem. A modem local to the computer system 1201 may receive thedata on the telephone line and use an infrared transmitter to convertthe data to an infrared signal. An infrared detector coupled to the bus1202 can receive the data carried in the infrared signal and place thedata on the bus 1202. The bus 1202 carries the data to the main memory1204, from which the processor 1203 retrieves and executes theinstructions. The instructions received by the main memory 1204 mayoptionally be stored on storage device 1207 or 1208 either before orafter execution by processor 1203.

The computer system 1201 also includes a communication interface 1213coupled to the bus 1202. The communication interface 1213 provides atwo-way data communication coupling to a network link 1214 that isconnected to, for example, a local area network (LAN) 1215, or toanother communications network 1216 such as the Internet. For example,the communication interface 1213 may be a network interface card toattach to any packet switched LAN. As another example, the communicationinterface 1213 may be an asymmetrical digital subscriber line (ADSL)card, an integrated services digital network (ISDN) card or a modem toprovide a data communication connection to a corresponding type ofcommunications line. Wireless links may also be implemented. In any suchimplementation, the communication interface 1213 sends and receiveselectrical, electromagnetic or optical signals that carry digital datastreams representing various types of information.

The network link 1214 typically provides data communication through oneor more networks to other data devices. For example, the network link1214 may provide a connection to another computer through a localnetwork 1215 (e.g., a LAN) or through equipment operated by a serviceprovider, which provides communication services through a communicationsnetwork 1216. The local network 1214 and the communications network 1216use, for example, electrical, electromagnetic, or optical signals thatcarry digital data streams, and the associated physical layer (e.g., CAT5 cable, coaxial cable, optical fiber, etc). The signals through thevarious networks and the signals on the network link 1214 and throughthe communication interface 1213, which carry the digital data to andfrom the computer system 1201 maybe implemented in baseband signals, orcarrier wave based signals. The baseband signals convey the digital dataas unmodulated electrical pulses that are descriptive of a stream ofdigital data bits, where the term “bits” is to be construed broadly tomean symbol, where each symbol conveys at least one or more informationbits. The digital data may also be used to modulate a carrier wave, suchas with amplitude, phase and/or frequency shift keyed signals that arepropagated over a conductive media, or transmitted as electromagneticwaves through a propagation medium. Thus, the digital data may be sentas unmodulated baseband data through a “wired” communication channeland/or sent within a predetermined frequency band, different thanbaseband, by modulating a carrier wave. The computer system 1201 cantransmit and receive data, including program code, through thenetwork(s) 1215 and 1216, the network link 1214, and the communicationinterface 1213. Moreover, the network link 1214 may provide a connectionthrough a LAN 1215 to a mobile device 1217 such as a personal digitalassistant (PDA) laptop computer, or cellular telephone.

The exemplary energy spectrum previously noted in FIG. 1 may also beused in this computer-implemented system.

The reagents and chemicals useful for methods and systems of theinvention may be packaged in kits to facilitate application of theinvention. In one exemplary embodiment, a kit would comprise at leastone activatable agent capable of producing a predetermined cellularchange, at least one energy modulation agent capable of activating theat least one activatable agent when energized, containers suitable forstoring the agents in stable form, and further comprising instructionsfor administering the at least one activatable agent and at least oneenergy modulation agent to a medium, and for applying an initiationenergy from an initiation energy source to activate the activatableagent. The instructions could be in any desired form, including but notlimited to, printed on a kit insert, printed on one or more containers,as well as electronically stored instructions provided on an electronicstorage medium, such as a computer readable storage medium. Alsooptionally included is a software package on a computer readable storagemedium that permits the user to integrate the information and calculatea control dose, to calculate and control intensity of the irradiationsource.

System Implementation

In one embodiment of the invention, there is provided a first system forproducing a change in a medium disposed in an artificial container. Thefirst system includes a mechanism configured to supply in the medium anactivatable agent. The system includes an initiation energy sourceconfigured to apply an initiation energy through the artificialcontainer to the medium to activate the at least one activatable agentin the medium.

In one embodiment, the energy modulation agent converts the appliedinitiation energy and produces light at an energy different from theapplied initiation energy. In one embodiment, the applied initiationenergy source is an external initiation energy source. In oneembodiment, the applied initiation energy source is a source that is atleast partially in a container holding the medium.

The medium in one embodiment is substantially transparent to theinitiation energy. For example, if the medium is a liquid or fluid foodproduct such as orange juice which has a substantial amount of suspendedsolids, then UV light for example as described above and even visiblelight will be substantially absorbed and/or scattered by the orangejuice medium. Furthermore, microwave energy will likewise be absorbed bythis medium. However, an initiation energy source such as an X-raysource will essentially transmit entirely through for example an orangejuice medium. The effect is the medium can now be totally illuminatedwith the external initiation energy source.

Other sources and tuned to specific wavelengths may also be used as theinitiation energy source. These sources would take advantage of an“optical window” in the medium where for example a particular wavelengthof light would not be absorbed. Water selectively scatters and absorbscertain wavelengths of visible light. The long wavelengths of the lightspectrum—red, yellow, and orange—can penetrate to approximately 15, 30,and 50 meters (49, 98, and 164 feet), respectively, while the shortwavelengths of the light spectrum—violet, blue and green—can penetratefurther. Thus, for many aqueous based systems, non-high energy X-raysources may not be needed. In those situations, energy modulation agentswould be added whose interaction with the incident light would producefor example photoactivation of catalysts in the aqueous medium.

Accordingly, depending on the medium and the energy modulation agent andthe activatable agent, the initiation energy source can include at leastone of an X-ray source, a gamma ray source, an electron beam source, anUV radiation source, a visible and infrared source, a microwave source,or a radio wave source. The initiation energy source can then be anenergy source emitting one of electromagnetic energy, acoustic energy,or thermal energy. The initiation energy source can then be an energysource emitting a wavelength whose depth of penetration penetratesthroughout the medium. The medium to be effected can be a medium to befermented, sterilized, or cold pasteurized. The medium to be effectedcan include bacteria, viruses, yeasts, and fungi.

The activatable agents can be photoactivatable agents such as thephotocages (described elsewhere) such that upon exposure to theinitiation energy source, the photocage disassociates rendering anactive agent available. The activatable agents can include agents suchas psoralens, pyrene cholesteryloleate, acridine, porphyrin,fluorescein, rhodamine, 16-diazorcortisone, ethidium, transition metalcomplexes of bleomycin, transition metal complexes of deglycobleomycinorganoplatinum complexes, alloxazines, vitamin Ks, vitamin L, vitaminmetabolites, vitamin precursors, naphthoquinones, naphthalenes,naphthols and derivatives thereof having planar molecular conformations,porphorinporphyrins, dyes and phenothiazine derivatives, coumarins,quinolones, quinones, and anthroquinones. The activatable agents caninclude photocatalysts such as TiO₂, ZnO, CdS, CdSe, SnO₂, SrTiO₃, WO₃,Fe₂O₃, and Ta₂O₅ particles.

The first system can include a mechanism configured to provide in themedium at least one energy modulation agent which converts theinitiation energy to an activation energy for activation of theactivatable agent(s). The energy modulation agent(s) can be a photonemitter such a phosphorescent compounds, chemiluminescent compounds, andbioluminescent compounds. The energy modulation agent(s) can be upconversion or down conversion agents. The energy modulation agent(s) canbe luminescent particles which emit light upon exposure to saidinitiation energy. The energy modulation agent(s) can be nanotubes,nanoparticles, chemilumiscent particles, and bioluminescent particles,and mixtures thereof. The luminescent particles can be chemiluminescentparticles which show enhanced chemiluminescence upon exposure tomicrowaves.

Depending on the initiation energy source, the system can include acontainer for the medium that is permeable to the applied initiationenergy. For example, for an X-ray source, the container can be made ofaluminum, quartz, glass, or plastic. For a microwave source, thecontainer can be made of quartz, glass, or plastic. Furthermore, thecontainer can be a container which receives and transmits the initiationenergy to fluid products to pasteurize the fluid products, or can be acontainer which receives and transmits the initiation energy to fluidproducts to remediate contaminants in the fluid products.

In another embodiment of the invention, there is provided a secondsystem for curing a radiation-curable medium. The second system includesa mechanism configured to supply an uncured radiation-curable mediumincluding at least one activatable agent which produces a change in theradiation-curable medium when activated, and further includes an appliedinitiation energy source configured to apply initiation energy to acomposition including the uncured radiation-curable medium and theenergy modulation agent. The energy modulation agent as described aboveabsorbs the initiation energy and converts the initiation energy to anactivation energy capable of curing the uncured medium (i.e., promotingpolymerization of polymers in the uncured medium). In another example,activation of the energy modulation agent produces a light whichactivates the at least one photoactivatable agent to polymerize polymersin the medium.

The second system has attributes similar to the first system describedabove and can further permit the at least one activatable agent toinclude a photoinitiator such as one of benzoin, substituted benzoins,alkyl ester substituted benzoins, Michler's ketone,dialkoxyacetophenones, diethoxyacetophenone, benzophenone, substitutedbenzophenones, acetophenone, substituted acetophenones, xanthone,substituted xanthones, benzoin methyl ether, benzoin ethyl ether,benzoin isopropyl ether, diethoxyxanthone, chloro-thio-xanthone,azo-bisisobutyronitrile, N-methyl diethanolaminebenzophenone,camphoquinone, peroxyester initiators, non-fluorene-carboxylic acidperoxyesters and mixtures thereof.

The second system can include a container for the uncuredradiation-curable medium that is permeable to the applied initiationenergy. The container can be configured to contain the uncuredradiation-curable medium or to hold a mold of the uncuredradiation-curable medium. The container as before can be an aluminumcontainer, a quartz container, a glass container, or a plasticcontainer, depending on the applied initiation energy.

In one embodiment, an energy source (e.g., an external energy source) isconfigured to irradiate the uncured radiation-curable medium in a jointregion (or regions) adhering one region of a utensil to another regionof the utensil. In another embodiment, the energy source is configuredto irradiate the joint regions and thereby induce sterilization of thejoint regions due to the production of internal UV light inside thejoint regions. In another embodiment, the energy source is configured toirradiate a surface coating.

The radiation-curable medium in the surface coating or in the mold or inother medium can include color pigments to add color to a finished curedproduct. The radiation-curable medium in the surface coating or in themold or in another medium can include fumed silica to promote strengthand enhance distribution of the internally generated light. Theradiation-curable medium in the surface coating or in the mold or inanother medium can include a moisture cure promoter to supplement thecure.

The second system provides one mechanism for production of novelradiation-cured articles, which include a radiation-cured medium and atleast one energy modulation agent distributed throughout the medium. Theenergy modulation agent being a substance which is capable of convertingan applied energy to light capable of producing a cure for theradiation-cured medium. The article can include luminescent particlessuch as for example nanotubes, nanoparticles, chemilumiscent particles,and bioluminescent particles, and mixtures thereof. The article caninclude chemiluminescent particles. The article can include colorpigments or fumed silica.

In another embodiment of the invention, there is provided a third systemfor producing a change in a medium disposed in an artificial container.The third system includes a mechanism configured to provide to themedium 1) an activatable agent and 2) at least one energy modulationagent. The energy modulation agent converts an initiation energy to anactivation energy which then activates the at least one activatableagent. The third system further includes an applied initiation energysource configured to apply the initiation energy through the artificialcontainer to activate the at least one activatable agent in the medium.

The third system has similar attributes to the first and second systemsdescribed above, and further includes encapsulated structures includingthe energy modulation agent. The encapsulated structures can includenanoparticles of the energy modulation agent encapsulated with apassivation layer or can include sealed quartz or glass tubes having theenergy modulation agent inside.

In another embodiment of the invention, there is provided a fourthsystem for producing a photo-stimulated change in a medium disposed inan artificial container. The fourth system includes a mechanismconfigured to provide in the medium at least one energy modulationagent. The energy modulation agent converts an initiation energy to anactivation energy which then produces the photo-stimulated change. Thefourth system further includes an initiation energy source configured toapply the initiation energy to the medium to activate the at least oneenergy modulation agent in the medium. The system can includeencapsulated structures including therein the energy modulation agent.The encapsulated structures can include nanoparticles of the energymodulation agent encapsulated with a passivation layer.

The fourth system can include a container which receives and transmitsthe initiation energy to products within the medium. The products caninclude plastics, where the activation energy alters the surfacestructure of the plastics. The products can include polylactic acid(PLA) plastics and polyhydroxyalkanoates (PHA) plastics. In thisembodiment, the activation energy can photo-graft a molecular speciesonto a surface of the plastics.

Sterilization Methods and System Components

Optical techniques have been often used in sterilization procedures torender unwanted or harmful waterborne microorganisms incapable ofreproducing using ultraviolet light (specifically the spectral area ofUV-C, 200 to 280 nm range). Ultraviolet light in the UV-C is consideredthe most lethal range as a germicidal disinfectant (capable of alteringa living microorganism's DNA, and keeping the microorganism fromreproducing). UV-C, with 264 nanometers being the peak germicidalwavelength, is known as the germicidal spectrum. Although the UV-Cmethod is simple and effective, it is not particularly effective insamples (gas, liquids, particulates) enclosed on containers which do nottransmit UV light. The present invention provides techniques and systemsthat can use externally applied radiation such as X-ray forsterilization. While illustrated below with respect to X-rayirradiation, and as discussed above, other suitable forms of energycould be used provided the containers and medium to be sterilized wassufficiently transparent for the medium to be thoroughly irradiated.Examples of alternative sources and materials for upconvertingluminescence to higher energies have been discussed above.

These systems are applicable in a number of the applications discussedabove and as well as in other sterilization areas. The systems couldthus be used in the waste water detoxification, blood sterilization,cold pasteurization, and photodeactivation commercial applicationsdiscussed in the sections above. These systems (like FIGS. 3B-3D) showthe use of artificial containers in which the medium to be treated isdisposed.

Having generally described this invention, a further understanding canbe obtained by reference to certain specific examples which are providedherein for purposes of illustration only and are not intended to belimiting unless otherwise specified.

Numerous modifications and variations of the invention are possible inlight of the above teachings. It is therefore to be understood thatwithin the scope of the appended claims, the invention may be practicedotherwise than as specifically described herein.

The invention claimed is:
 1. A method for curing an adhesive,comprising: disposing in contact with an object an adhesive compositioncomprising 1) an uncured radiation-curable medium, 2) an energymodulation agent, and 3) a photo-activated photoinitiator, wherein theenergy modulation agent is resistant to chemical interaction with theuncured radiation-curable medium; applying energy from at least one ofx-rays, gamma rays, or an electron beam into the composition, whereinthe energy interacts with the energy modulation agent and internallygenerates light inside the uncured radiation-curable medium; andactivating the photoinitiator in the radiation-curable medium with theinternally generated light and thereby curing the radiation-curablemedium.
 2. The method of claim 1, wherein the adhesive composition insaid disposing step comprises a chemically inert energy modulationagent.
 3. The method of claim 2, wherein the disposing comprisesdisposing a polymer coated energy modulation agent as the chemicallyinert energy modulation agent.
 4. The method of claim 2, wherein thedisposing comprises disposing a silica coated energy modulation agent asthe chemically inert energy modulation agent.
 5. The method of claim 2,wherein the disposing comprises disposing a zeolite-encased energymodulation agent as the chemically inert energy modulation agent.
 6. Themethod of claim 2, wherein the disposing comprises disposing at leastone of a telluride, a selenide, and an oxide semiconductor as thechemically inert energy modulation agent.
 7. The method of claim 2,wherein the disposing comprises disposing at least one of Y₂O₃; ZnSe;Mn, Er ZnSe; Mn; Mn, Yb ZnSe; Mn, Y₂O₃:Tb^(3+; Y) ₂O₃:Tb³⁺, Er3⁺; CdSe,Y₂O₃:Eu³⁺, Y₂O₃:Eu³⁺; BaFBr:Tb³⁺; and YF₃:Tb³⁺ as the chemically inertenergy modulation agent.
 8. The method of claim 1, wherein the disposingcomprises disposing an adhesive composition having a concentration of10⁹ nanoparticles/cm³ of 200 nm diameter energy modulation agents. 9.The method of claim 2, wherein the disposing comprises disposing anadhesive composition having a concentration greater than 10⁹nanoparticles/cm³ of 200 diameter energy modulation agents.
 10. Themethod of claim 1, wherein the activating comprises: activating thephotoiniator with 200-280 nm wavelength ultraviolet light.
 11. Themethod of claim 1, wherein the activating comprises: activating thephotoiniator with 280-320 nm wavelength ultraviolet light.
 12. Themethod of claim 1, wherein the activating comprises: activating thephotoiniator with 320-400 nm wavelength ultraviolet light.
 13. Themethod of claim 1, wherein the activating comprises: activating thephotoiniator with 350-400 nm wavelength ultraviolet light.
 14. Themethod of claim 1, wherein the uncured radiation-curable mediumcomprises a UV-curable silicone.
 15. The method of claim 14, wherein theUV-curable silicone comprises an organopolysiloxane.
 16. The method ofclaim 14, wherein the UV-curable silicone includes a methacrylate group.17. The method of claim 14, wherein the UV-curable silicone includes anacryloxy group.
 18. The method of claim 14, wherein the UV-curablesilicone includes at least one of carboxylate, maleate, and cinnamate.19. The method of claim 14, wherein the UV-curable silicone includes afree radical generator.
 20. The method of claim 19, wherein the freeradical generator comprises a benzoin ether.
 21. The method of claim 14,wherein the UV-curable silicone includes at least one of trimethylsilyl,dimethylsilyl, phenyldimethylsilyl, vinyldimethylsilyl,trifluoropropyldimethylsilyl, (4-vinylphenyl)dimethylsilyl,(vinylbenzyl)dimethylsilyl, and (vinylphenethyl)dimethylsilyl.
 22. Themethod of claim 1, wherein the photoinitiator comprises at least one ofat least one of benzoin, substituted benzoins, alkyl ester substitutedbenzoins, Michler's ketone, dialkoxyacetophenones, diethoxyacetophenone,benzophenone, substituted benzophenones, acetophenone, substitutedacetophenones, xanthone, substituted xanthones, benzoin methyl ether,benzoin ethyl ether, benzoin isopropyl ether, diethoxyxanthone,chloro-thio-xanthone, azo-bisisobutyronitrile, N-methyldiethanolaminebenzophenone, camphoquinone, peroxyester initiators,non-fluorene-carboxylic acid peroxyesters and mixtures thereof.
 23. Themethod of claim 1, wherein the photoinitiator comprises a weightpercentage of the uncured radiation-curable medium ranging from 0.1% to10%.
 24. The method of claim 1, wherein the photoinitiator comprises aweight percentage of the uncured radiation-curable medium ranging from 2to 6%.
 25. The method of claim 1, wherein the uncured radiation-curablemedium includes a moisture cure catalyst.
 26. The method of claim 22,wherein the moisture cure catalyst comprises an organic compound of atleast one of titanium, tin, zirconium, and combinations thereof.
 27. Themethod of claim 1, wherein the uncured radiation-curable medium includesan inorganic filler material.
 28. The method of claim 24, wherein theinorganic filler material comprises a silica.
 29. The method of claim24, wherein the inorganic filler material comprises a color pigment. 30.The method of claim 1, wherein the uncured radiation-curable mediumincludes a UV curable urethane acrylate.
 31. The method of claim 1,wherein the applying energy comprises: applying said energy from anexternal energy source of the x-rays, gamma rays, or electron beam. 32.The method of claim 1, wherein the applying energy comprises: applying10 to 150 keV x-rays to the uncured radiation-curable medium.
 33. Themethod of claim 1, wherein the applying energy comprises: applying saidenergy from a directed or focused energy source.
 34. The method of claim1, wherein the energy modulation agent comprises luminescent particlesdistributed throughout the uncured medium whose emission cures theuncured medium throughout the medium.
 35. The method of claim 1, furthercomprising: filling a gap inside the object and curing theradiation-curable medium in the gap.
 36. The method of claim 35, whereinthe gap is inside the object.
 37. The method of claim 36, wherein theobject comprises at least one of a bottle cap, a prosthetic device, aconcrete structure, and a storage tank.
 38. The method of claim 1,wherein the disposing comprises pressure injecting said composition intosaid object to fill a gap inside the object.
 39. The method of claim 1,wherein the curing the radiation-curable medium comprises closing a holeor a pathway in the object.
 40. The method of claim 1, wherein theactivating comprises adhering said first object to a second object. 41.The method of claim 40, wherein the first object comprises a medicalbottle cap and the second object comprises a seal material for themedical bottle cap.